1. Field of the Invention
The present invention relates to a pharmaceutical composition for the prevention and treatment of inflammatory disease or asthma comprising the extract of Decaspermum fruticosum as an active ingredient.
2. Description of the Related Art
Inflammation is defined by the pathological state of abscess formed by the invasion of foreign source of infection such as bacteria, fungi, viruses, and other allergens. Particularly, when foreign bacteria invade in a specific tissue and proliferate therein, leukocytes recognize them and attack the proliferating bacteria actively. In the course, the dead leukocytes are accumulated in the tissue invaded by the bacteria along with the cell lysate resulted from the dead bacteria attacked by the leukocytes, leading to the formation of abscess. The treatment of abscess resulted from inflammation is focused on the anti-inflammation action. Anti-inflammatory action indicates the action inhibiting the proliferation of the invading bacteria using an anti-bacterial agent or the action promoting anti-inflammation by activating macrophages or increasing the functions of macrophages eating foreign materials accumulated in abscess to help the digestion and elimination of such invaders.
In general, inflammatory response is a defense mechanism for the recovery and regeneration of the tissues damaged by invasion causing structural changes, in which local blood vessels, various tissue cells, and immune cells are involved. The inflammatory response induced by the invasion of a foreign material is a normal defense mechanism to protect the living things. However, the inflammatory response induced abnormally or excessively can cause various diseases that are called inflammatory disease. Inflammatory disease is the disease that might put human in danger by amplifying or continuing inflammation with various inflammatory mediators secreted in target cells activated by external stimuli, which is exemplified by acute inflammation, joint disease including rheumatoid arthritis, skin disease including psoriasis, and allergic disease including bronchial asthma, etc.
Asthma is the disease characterized by bronchial hyper-sensitivity reacting to various stimuli, whose clinical symptoms are wheezing, dyspnea, and coughing caused by broad narrowness in the airway. In general, such symptoms can be improved naturally or by the treatment. In most cases, asthma is allergic reaction which is characterized by chronic airway inflammation and bronchial hyper-responsiveness (Minoguchi K and Adachi M. Pathophysiology of asthma. In: Cherniack N S, Altose M D, Homma I, editors. Rehabilitation of the patient with respiratory disease. New York: McGraw-Hill, 1999, pp 97-104).
Asthma is mainly divided into two groups, which are extrinsic asthma and intrinsic asthma. Extrinsic asthma develops symptoms by the exposure on allergens. Extrinsic asthma can be diagnosed when skin test or bronchial challenge test is positive on a certain allergen and is commonly observed in young age group. The major causes of extrinsic asthma are house dust and dust mice, and other minor causes are exemplified by pollen, animal epithelium, and fungi. Intrinsic asthma is induced or worsened by upper airway infection, exercise, anxiety, cold climate, and humidity change, which is usually observed among adults. There are examples of other asthma such as drug induced asthma, exercise induced asthma, and occupational asthma, etc.
Asthma is generally understood as a chronic inflammatory disease that is caused by the migration and infiltration of inflammatory cells in the airway and in tissues around the airway that have been proliferated, differentiated, and activated by interleukin-4, -5, and -13 produced by TH2 immune cells (Elias J A, et al., J. Clin. Invest., 111, pp 291-297, 2003). In that case, activated inflammatory cells such as activated neutrophils, mast cells, and alveolar macrophages secrete various inflammatory mediators (cysteine, leukotriene, and prostaglandin) to play an important role in strong bronchoconstriction reaction (Maggi E., Immunotechnology, 3, pp 233-244, 1998; Pawankar R., Curr. Opin. Allergy Clin. Immunol., 1, pp 3-6, 2001; Barnes P J, et al., Pharmacol Rev., 50, pp 515-596, 1998).
The production of cytokines such as IL-4, IL-5 and IL-13, and immunoglobulin E involved in the activation of inflammatory cells and biosynthesis of cysteine leukotriene secreted in inflammatory cells including eosinophils mediated by the said production are key factors causing inflammation and allergic reaction that can be resulted in asthma. Therefore, attempts have been made to develop novel drugs to inhibit the production of cytokines and immunoglobulin E.
A variety of asthma drugs have been used nowadays but many of them have side effects that have to be carefully considered. Inhaling type corticosteroid is still the most important asthma treating drug with excellent effect. However, when the corticosteroid is used for a long term, serious side effects such as adrenal suppression, decreased bone mineral density, growth trouble, and complications in eyes and skin are developed. In a previous report, corticosteroid allegedly increases collagen synthesis (Warshmana G S, et al., Am J Physiol 274, 499-507, 1998). Even after many years of treatment with corticosteroid, the chance of normalization in bronchial hyper-responsiveness in chronic asthma patients is very rare. Long term administration of beta-2 agonist is not very effective in inhibiting airway remodeling, either (Jeffery P K, et al., Am Rev Respir Dis 145: 890-0, 1992). Continuous administration of beta-2 agonist such as salmeterol and formeterol can prevent asthma exacerbation but at the same time can cause death of asthma patient. Even though such side effects have been continuously reported, the drug has been still prescribed based on the belief that the asthma relieving effect is greater than the risk of side effects. The growth rate of children asthma patients who are relatively sensitive to side effects was measured. As a result, the growth rate of children asthma patients treated with oral leukotriene antagonist (montelukast) was greater by 1 cm/year than the growth rate of children asthma patients treated with inhaling type corticosteroid (Garcia Garcia ml, et al., Pediatrics 116(2): 360-9, 2005). If asthma is not treated properly in the growth period, not only the lung but also overall body growth can be inhibited or damaged. So, it is necessary to maintain normal healthy lung function with steady treatment. It has been confirmed to be more important to control inflammation in the airway by using a safe drug for the long term treatment. Thus, it is also important to consider the asthma relieving effect and side effects altogether before choosing an asthma treating drug. Leukotriene antagonist has been known to have low chances of side effects, so that it has been constantly prescribed for the prevention and long term treatment for asthma. However, asthma treating effect of it is weaker than other drugs, demonstrating only one third of asthma patients is improved. Therefore, it is still requested to develop a novel asthma treating agent that is safe without toxicity and does not cause drug resistance.
Decaspermum fruticosum is a short shrub having thin leaves facing each other. It has light pink flowers and purple fruits bearing lots of seeds. This shrub is widely distributed in Burma, Australia, and pacific islands. It flourishes in volcanic soils. Reports have already been made saying that a cosmetic composition comprising herb extract in addition to the extract of Decaspermum fruticosum can improve dry skin to be moisturized and creamy skin (Ohara, Mitsuharu & Hori, Michimasa, JP 2001220312). It has also been reported that young leaves and flower ear extracts of this shrub are effective in making hair grow and darker. However, the anti-inflammatory effect and anti-asthma effect of this plant have not been disclosed, yet.
The present inventors have tried to develop a novel drug to treat inflammatory disease or asthma using natural substances. As a result, the inventors confirmed that the extract of Decaspermum fruticosum reduced inflammatory cells, immunoglobulins, and chemokines in bronchoalveolar lavage fluid of airway-sensitized mouse model, and inhibited inflammatory response induced by lipopolysaccharide in vitro. The present inventors thus completed this invention by further confirming that the extract of Decaspermum fruticosum could be effectively used as an active ingredient of a preventive and therapeutic agent for inflammatory disease or asthma.